We evaluated the capacity of metallothioneins (MT) in maintaining anaerobic metabolism in the green lipped mussel Perna viridis during experimentally induced oxidative stress. Mussels were exposed to 50 μg/L of cadmium during seven days, followed by recuperation in the sea during 35 days. Other groups of cadmium pre-exposed organisms and their respective controls were exposed to 200 and 500 mM of ferric iron/100 mM ascorbate to promote the formation of reactive oxygen species (ROS) by the Fenton reaction. Oxidative damage was evidenced by the malondialdehyde (MDA) production through thiobarbituric acid reactive substances (TBARS). The activities of the enzymes, hexokinase (HK), piruvate kinase (PK), and glucose-6-P dehydrogenase (G6PDH) in the digestive gland and the survival during anoxia were evaluated. Exposure of organisms to cadmium led to a significant bioaccumulation of this metal with concomitant high MT levels. Survival during prolonged periods of anoxia was reduced only in the iron/ascorbate exposed organisms, which exhibited an increase in MDA concentration; however, the cadmium-preexposed and control organisms showed similar resistance to anoxia. The iron/ascorbate-exposed organisms showed a decrease in the activities of HK in the cytosol and HK, PK, and G6PDH of the particulate fraction. In comparison with the control group, the cadmium pre-exposed/iron-exposed organisms did not show significant differences in lipid peroxidation, associated with elevated MT levels. In conclusion, the data obtained suggest that of the glycolytic enzymes, HK and PK and G6PDH are targets to the attack by ROS and that the MT can protect molecules against these effects. MT appears to protect against ROS induced injury, allowing maintenance of metabolic control by glycolytic enzymes that are important during anaerobic metabolism.